Realising the therapeutic potential of the human microbiota in metastatic pancreatic ductal adenocarcinoma

Abstract

Treatment options for metastatic pancreatic ductal adenocarcinoma (mPDAC) patients remain limited, meaning that death within weeks of diagnosis unfortunately remains a common occurrence. Whilst metastases from other malignancy sites, such as colorectal and breast, are amenable to resection in selected patients, consensus remains largely against resection of mPDAC. Without surgical resection, chemotherapy remains the main treatment option and despite advances in regimens, a large proportion of mPDAC patients do not respond to these treatments. Understandably, investigation into whether different genetic subtypes of PDAC can explain the changes in response to chemotherapy have been carried out but as yet has not demonstrated any marked differences between those that do and do not respond to chemotherapy treatment.This review outlines the emerging role that both the gut and tumour microbiome play in modulating the progression of PDAC, ranging from chemosensitivity to immune infiltration of the tumour This puts the gut microbiome in a promising position as a potential future therapeutic route for mPDAC patients. Possible methods to modulate the gut and tumour microbiome include antibiotics, probiotics and faecal microbiota transplantation (FMT). The next steps should therefore be to focus upon how we can effectively and safely introduce these beneficial bacteria into the gut and tumour microbiome of mPDAC patients through clinical trials.

Keywords

• Pancreatic ductal adenocarcinoma
• Metastases
• Gut microbiome
• Tumour microbiome